Comparing Angiomax to Heparin With Protamine Reversal in Patients OPCAB (OPCAB)

• ClinicalTrials.gov Identifier: NCT00073593
• Recruitment Status: Completed
• First Posted: November 27, 2003
• Last Update Posted: November 10, 2011
• Sponsor: The Medicines Company
• Information provided by (Responsible Party): The Medicines Company

Study Description

Brief Summary:

The purpose of this study is to examine the safety and efficacy of Angiomax as an alternative anticoagulant to heparin with protamine reversal in patients undergoing off-pump coronary artery bypass graft surgery.

Condition or disease	Intervention/treatment	Phase
Cardiac Surgery; Coronary Artery Bypass Surgery	Drug: Bivalirudin; Drug: Heparin; Drug: Protamine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study Comparing Angiomax (Bivalirudin) to Heparin With Protamine Reversal in Patients Undergoing Coronary Artery Bypass (OPCAB) Surgery
• Study Start Date: August 2003
• Actual Primary Completion Date: May 2004

Arms and Interventions

Arm	Intervention/treatment
Experimental: bivalirudin; 250mg vial given as 0.75mg/kg intravenous (IV) bolus and 1.75 mg/kg/hr IV infusion for the duration of the procedure with the option to increase or decrease the infusion in 0.25 mg/kg/hr increments or to administer additional 0.1-0.5 mg/kg boluses to maintain an ACT>300 seconds.	Drug: Bivalirudin; 250 mg vial administered as 0.75 mg/kg intravenous (IV) bolus and 1.75 mg/kg/h IV infusion for the duration of surgery with the option to increase or decrease the infusion in 0.25 mg/kg/h increments or to administer additional 0.1-0.5 mg/kg boluses to maintain an activated clotting time (ACT) >300 seconds (s).
Active Comparator: heparin/protamine; 1.5-3.5 mg/kg (200-400 U/kg) intravenous (IV) bolus to target an ACT >300 seconds followed by weight-adjusted boluses as needed during the procedure to achieve/maintain the target ACT. Protamine as needed	Drug: Heparin; : Per institutional practice, at 1.5-3.5 mg/kg (200-400 U/kg) IV bolus to achieve a target ACT of >300 s followed by weight-adjusted boluses as needed during surgery to achieve/maintain the target ACT. Batches from hospital stock.; Drug: Protamine; Per institutional practice. Batches from hospital stock.

Outcome Measures

Primary Outcome Measures :

1. Death [ Time Frame: Hospital discharge or Day 7 ]
2. Q-wave MI [ Time Frame: hospital discharge or day 7, ]
3. Repeat Coronary Revascularization, [ Time Frame: hospital discharge or day 7, ]
4. Stroke (hemorrhagic or ischemic). [ Time Frame: hospital discharge or day 7 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion:

• Provide written informed consent before initiation of any study related procedures.
• Be at least 18 years of age.
• Be accepted for elective off-pump coronary artery bypass graft (CABG) surgery without concomitant cardiac surgical procedures.
• < 4 planned Coronary Artery Bypass Grafts

Exclusion:

• Any prior Cardio-Thoracic Surgical procedures requiring median sternotomy
• Confirmed pregnancy - baseline urine or serum pregnancy test (if woman of childbearing potential).
• Cerebrovascular accident within 6 months before randomization, or any cerebrovascular accident with residual neurological deficit.
• Intracranial neoplasm, arteriovenous malformation, or aneurysm.
• Dependency on renal dialysis or creatinine clearance <30mL/min.
• Ongoing treatment with warfarin (or other oral anticoagulants) at the time of randomization. Patients previously treated with warfarin may be enrolled if warfarin therapy can be safely discontinued and baseline INR is <1.3 times control in the absence of heparin therapy.
• Known allergy to Angiomax or hirudin derived drugs, or known sensitivity to any component of these products.
• Patients receiving clopidogrel within the previous 5 days of randomization.
• Patients receiving a glycoprotein IIb/IIIa inhibitor within 48 hours if abciximab (ReoPro) or within 24 hours if eptifibatide (Integrilin) and tirofiban (Aggrastat) of randomization
• Patients receiving lepirudin or argatroban within the previous 24 hours of randomization.
• Patients receiving low molecular weight heparin (LMWH) or thrombolytics within the previous 12 hours or unfractionated heparin within 30 minutes of randomization.
• Patients with active or prior history of heparin-induced thrombocytopenia (HIT)/heparin-induced thrombocytopenia and thrombosis syndrome (HITTS)*.
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of randomization.
• Refusal to undergo blood transfusion should it become necessary.
• Any other disease or condition, which, in the judgment of the investigator would place a patient at undue risk by being enrolled in the trial or inability to comply with study requirements.

Contacts and Locations

Locations

United States, Ohio

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

The Medicines Company

Investigators

• Study Director: Andrew Sternlicht, MD; The Medicines Company

More Information

• Responsible Party: The Medicines Company
• ClinicalTrials.gov Identifier: NCT00073593
• Other Study ID Numbers: TMC-BIV-02-07; EVOLUTION
• First Posted: November 27, 2003
• Last Update Posted: November 10, 2011
• Last Verified: November 2011

Keywords provided by The Medicines Company:

Off-Pump Coronary Artery Bypass Graft Surgery; CABG; OPCAB; Heparin; Patients requiring off-pump CABG

Additional relevant MeSH terms:

Heparin; Calcium heparin; Hirudins; Benzocaine; Bivalirudin; Protamines; Anesthetics, Local; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Heparin Antagonists; Coagulants